PROJECT SUMMARY & ABSTRACT Financial toxicity (FT), a term used to describe the high cost and cost-related psychosocial burden that cancer care places on patients and their families, is a major and underappreciated problem affecting at least 20% of all cancer patients, with potentially devastating effects on outcomes. FT disproportionately affects patients in rural settings due to multiple socioeconomic, access, and clinical factors. A recent review of cancer-related financial hardship characterized the burden of FT as belonging to one of three domains: (1) material hardship, including high out-of-pocket expenses and lost wages; (2) psychological burden from distress and anxiety caused by high cancer costs; and (3) behavioral changes resulting from high cancer care costs, including changes in both medical and non-medical spending. Across cancer sites and stages, the considerable material hardship caused by cancer has been linked consistently to negative psychological and behavioral outcomes, including lower health-related quality of life, higher emotional distress, treatment delay/discontinuation, and filing for bankruptcy. Importantly, FT is also associated with increased mortality. Harmful psychological effects and care-altering behavioral responses, such as delaying or foregoing treatment, are more common in rural patients who also face considerable geographic barriers to care and greater financial vulnerability (e.g., lack of health insurance), likely contributing to widely-observed rural/urban disparities in cancer mortality. Interventions are urgently needed to prevent and mitigate high FT for cancer patients living in rural areas. Our prior work with patients, cancer care professionals, and a regional network of rural oncology practices argues strongly for intervening with financial navigation (FN), due to the complex material, structural, and psychological needs in this setting, fragmentation of existing financial support resources, and complicated assistance eligibility requirements. FN is one type of evidence-based intervention implemented at the practice or system level that can identify patients at high risk for FT, assess eligibility for existing federal, nonprofit, manufacturer, and local financial support resources, clarify treatment cost expectations, and develop strategies to cope with high costs of care. Our long-term goal is to improve cancer care delivery, reduce FT, and improve outcomes in underserved, rural populations through sustainable, scalable interventions. The objectives of this application are to: (1) understand the rural oncology practice context to optimize tailored strategies to support FN implementation; (2) assess FN intervention implementation in rural oncology practices; and (3) evaluate the effects of FN implementation on patient outcomes, including FT and health-related quality of life, in rural oncology practices. Our proposal is directly responsive to RFA-CA-18-026, which seeks to ?improve the reach and quality of cancer care in rural populations?. Expected outcomes are the development and refinement of the operational and logistical processes needed to deliver effective FN in rural settings and reduction in FT, with potential to reduce rural outcome disparities.